1. Field of the Invention
The present invention relates to a method of producing an optically active β-aminocarbonyl compound by an asymmetric Mannich-type reaction using a column reactor.
2. Description of the Related Art
A proline and a derivative thereof have been found to act as an organocatalyst in an organic synthesis. In particular, the proline and derivative thereof have advantages in which an optically active proline skeleton can be easily obtained, a metal is not used, and a usage environment is not limited. It has been known that an optically active syn-β-aminocarbonyl compound is obtained at high yield with high enantioselectivity by a catalytic activity of such a proline in a homogeneous liquid-phase Mannich-type reaction effective for the synthesis of a pharmaceutical raw material, or the like (Patent Literature 1). However, in the homogeneous liquid-phase Mannich-type reaction, it is difficult that the proline derivative as the catalyst is removed from the reaction mixture at low cost. For this reason, the formation of a solid-phase catalyst from the proline derivative has been proposed. For example, the following technique has been proposed (Non-Patent Literature 1). A monomer composition containing an acrylate derivative monomer having a proline structure in the molecule, an unsaturated compound such as styrene and divinylbenzene, and a radical polymerization initiator is subjected to suspension polymerization, to obtain resin particles. A solution of carbonyl compound having an α-hydrogen is placed in a reaction vessel, and the resin particles as asymmetric solid-phase catalyst particles are added thereto. The reaction mixture is heated under uniform mixing to obtain an aldol reaction product through a batch process. It is considered that this technique is applied to an asymmetric Mannich-type reaction.